Piperidine, 4-[4-[(1R)-[4-(trifluoromethyl)phenyl]-2-methoxyethyl]-(3S)-methyl-1-piperazinyl]-4-methyl-1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl] (Formula I) is disclosed in pending U.S. patent application, Ser. No. 09/562,814 filed on May 1, 2000, incorporated herein by reference.

That patent application, Ser. No. 09/562,814, discloses several novel antagonists of the CCR5 receptor which are useful for the treatment of AIDS and related HIV infections, including the compound of Formula I. CCR-5 receptors have also been reported to mediate cell transfer in inflammatory diseases such as arthritis, rheumatoid arthritis, atopic dermatitis, psoriasis, asthma and allergies, and inhibitors of such receptors are expected to be useful in the treatment of such diseases, and in the treatment of other inflammatory diseases or conditions such diseases, and in the treatment of other inflammatory diseases or conditions such as inflammatory bowel disease, multiple sclerosis, solid organ transplant rejection and graft v. host disease.
Generally, pharmaceutical compounds are used as their pharmaceutically acceptable salts. This is true of CCR5 receptor antagonists such as the compound of Formula I too, which makes the preparation of pharmaceutically acceptable salts of such compounds quite important.
The compound of Formula I has two chiral centers and the absolute configurations of the chiral centers are controlled by the chemical synthesis. However, the compound of Formula I exists as a mixture of rotational isomers or rotamers. There are two rotamers (diastereoisomers) resulting from restricted rotation about the amide bond marked in the figure in Scheme 1. The two rotamers may be denoted as isomers 1 and 2, in order of their elution from a HPLC column (Scheme 1):
While general synthetic approaches for salts typically yield a 1:1 ratio of the rotamers 1 and 2, it would be preferable to find methods of synthesis that would yield rotamer populations that are enriched in certain rotamers preferentially.